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This technology includes compounds, pharmaceutical compositions and methods of treating or preventing neurological or psychiatric disorders for which inhibiting KCNH2-3.1 containing potassium channels provides a therapeutic effect. Polymorphisms in the KCNH2 gene have been associated with altered cognitive function and schizophrenia. The KCNH2 gene encodes the protein which forms the human ether-a-go-go related (hERG) voltage-gated potassium channel 4, 5.

This technology includes a newly discovered molecule 2,6-Dimethoxy-4-(5-Phenyl-4-Thiophen-2-yl-1H-Imidazol-2-yl)-Phenol (DPTIP) as potent inhibitor of neutral sphingomyelinase 2 (nSMase2), to be used for the treatment of neurodegenerative and oncologic diseases. This discovery was identified through unbiased screening of the National Center for Advancing Chemical Sciences (NCATS) chemical library using our human neutral sphingomyelinase assay.

This technology includes a new chemical series of substituted bicyclic heteroaryl small molecules as potent bromodomain-containing protein BRD4 inhibitors used for the treatment of cancer and inflammatory diseases. The optimization led to compounds with good potency in enzymatic assay ( 100 nM) and in MV4-11 cell-based assay ( 1000 nM) as well as excellent early ADME properties. We also identified N-methyl 2 pyridone and N-methyl pyrrolopyridone are great replacements of di-methylisoxazole. This chemical series also exhibited good ADME profiles, including PK.

This technology includes the identification of small molecule inhibitors of nuclear factor erythroid-2 related factor-2 (Nrf2) as therapeutic anticancer agents. Multiple mechanisms lead to frequent dysregulation of Nrf2 activity in cancer cells, which promotes both tumorigenesis and therapeutic resistance. Dysregulated Nrf2-Keap1 pathway is a novel determinant of chemoresistance/radioresistance and inhibition of Nrf2 signaling will enhance the efficacy of chemotherapeutic and radiotherapy.

This technology includes methods for the biofabrication of full thickness skin tissues in 12, 24, 48 and 96-well plates, using commercially available hardware to enable the implementation of large-scale toxicity and efficacy testing of chemical and biologics.

This technology includes a novel chemotype against mutant (R 132H) isocitrate dehydrogenase 1 (IDH1) enzyme to be utilized as an anticancer therapy. We have progressed the structure activity relationship (SAR) and optimized the compound to be low nanomolar inhibitor of the enzyme with low nanomolar inhibition of the target in cells. These compounds lower 2-hydroxyglutarate, which has been termed an 'oncometabolite' and is common in a subset of cancers including glioma, cholangiocarcinoma, chondrosarcoma and acute myeloid leukemia.

This technology includes mutant isocitrate dehydrogenase (IDH1) inhibitors to be utilized as anticancer therapy. These potent inhibitors are aimed at lowering levels of the oncometabolite–2-hydroxyglutarate.

This technology includes a family of inhibitors of 3-phosphoglycerate dehydrogenase (PHGDH) which could be utilized as a treatment for cancer. These compounds are based on a carbiothioamide core and represent the first chemotype capable of inhibiting this enzyme. The compounds have in vitro IC50s of 1-5 uM and exhibit selective cytotoxicity towards PHGDH-overexpressing cell lines of ~10 uM. They exhibit at least an order of magnitude lower toxicity towards cell lines that do not express PHGDH.

This technology includes selective inhibitors of the human enzyme galactokinase (EC 2.7.1.6), which may be useful for the treatment of Galactosemia and other diseases caused by aberrant galactose metabolism, including cancer. These compounds inhibit the first step in galactose metabolism, thereby eliminating the build-up of toxic metabolites during the aberrant metabolism of galactose, as well as inhibitor the entry of galactose into glycolysis and other downstream assays.

This technology includes the identification and use of heterocyclic alcohol compounds, including RITA and N-BIC, for the treatment of SULT1A1-expression cancers. A high-throughput screen (qHTS) was performed using >1,000 caner cell lines identified a compound called YC-1 (also called Lificiguat) that is effective across cancer cell types that express the phase 2 detoxifying enzyme SULT1A1.